While encompassing a relatively wide group of organisms, opportunistic infections represent a major problem in clinical medicine today. The microorganisms causing these infections usually although not exclusively do not cause significant disease in immunologically competent individuals but become life-threatening in individuals who are immunocompromised or comprised in some other fashion s to their ability to eliminate an infectious agent. Many of the opportunistic agents are difficult to treat because they have high levels of antibiotic resistance, are affected only by relatively toxic antimicrobials or have not available treatment. In recent years there has been a major "epidemic" of opportunistic infections with the advent of th routine transplantations of bone marrow and organs, the dramatic increase in AIDS, and the continued existence of various malignancies and disorders such as cystic fibrosis. It is the overall goal of this proposal to establish a center for the study of opportunistic infections to facilitate the extension of basic studies on the pathogenesis and virulence of opportunistic organisms to their application in a clinical setting to aid in the diagnosis, assessment of potential virulence, determination of antibiotic susceptibility, and the study of epidemiology. Five different opportunistic organisms will be studied in the context of this proposal, Mycobacteria, Pseudomonas, Staphylococcus, Herpes Simplex and Varicella zoster. Specific goals of the program are as follows: 1. To develop a critical mass of competitive extramurally funded investigators with expertise in the study of the pathogenesis of opportunistic infections. 2. To promote an facilitate basic science and clinical interactions to develop new areas of clinically-based research in opportunistic infections. 3. To create a core Molecular Resource laboratory which will facilitate the application of basic research to the clinical setting. 4. To provide a research training environment for residents, clinical fellows and junior clinical faculty in opportunistic infections as they pertain to HIV, cystic fibrosis, cancer and transplantation.